World Journal of Urology

, Volume 29, Issue 1, pp 35–41

Long-term urinary adverse effects of pelvic radiotherapy

Topic Paper

Abstract

Objective

Radiation for tumors arising in the pelvis has been utilized for over a 100 years. Adverse effects (AEs) of radiotherapy (RT) continue to accumulate with time and are reported to show decades after treatment. The benefit of RT for pelvic tumors is well described as is their acute AEs. Late AEs are less well described. The burden of treatment for the late AEs is large given the high utilization of RT.

Review

For prostate cancer, 37% of patients will receive radiation during the first 6 months after diagnosis. Low-and high-grade AEs are reported to occur in 20–43 and 5–13%, respectively, with a median follow-up of ~60 months. For bladder cancer, the grade 2 and grade 3 late AEs occur in 18–27 and 6–17% with a median follow-up of 29–76 months. For cervical cancer, the risk of low-grade AEs following radiation can be as high as 28%. High-grade AEs occur in about 8% at 3 years and 14.4% at 20 years or ~0.34% per year. Radiation AEs appear to be less common or at least less well studied after radiation for rectal and endometrial cancers.

Conclusion

Properly delineating the rate of long-term AEs after pelvic RT is instrumental to counseling patients about their options for cancer treatment. Further studies are needed that are powered to specifically evaluate long-term AEs.

Keywords

Radiotherapy Pelvic cancers Prostate cancer Bladder cancer Cervical cancer Endometrial cancer Rectal cancer Radiation adverse effects Hemorrhagic cystitis Urethral strictures Ureteral strictures 

References

  1. 1.
    Cancer Facts & Figures 2009 (2009) American Cancer Society, AtlantaGoogle Scholar
  2. 2.
    Elliott SP, Jarosek SA, Virnig BA. Unpublished analysis of SEER public use file 1992–2006Google Scholar
  3. 3.
    Crew JP, Jephcott CR, Reynard JM (2001) Radiation-induced haemorrhagic cystitis. Eur Urol 40:111–123CrossRefPubMedGoogle Scholar
  4. 4.
    deVries CR, Freiha FS (1990) Hemorrhagic cystitis: a review. J Urol 143:1–9PubMedGoogle Scholar
  5. 5.
    Elliott SP, Meng MV, Elkin EP, McAninch JW, Duchane J, Carroll PR (2007) Incidence of urethral stricture after primary treatment for prostate cancer: data from CaPSURE. J Urol 178:529–534 (discussion 34)CrossRefPubMedGoogle Scholar
  6. 6.
    Fujikawa K, Miyamoto T, Ihara Y, Matsui Y, Takeuchi H (2001) High incidence of severe urologic complications following radiotherapy for cervical cancer in Japanese women. Gynecol Oncol 80:21–23CrossRefPubMedGoogle Scholar
  7. 7.
    Gellrich J, Hakenberg OW, Oehlschlager S, Wirth MP (2003) Manifestation, latency and management of late urological complications after curative radiotherapy for cervical carcinoma. Onkologie 26:334–340CrossRefPubMedGoogle Scholar
  8. 8.
    Common Terminology Criteria for Adverse Events, Version 4.0. In: National Cancer InstituteGoogle Scholar
  9. 9.
    Cox JD, Stetz J, Pajak TF (1995) Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European organization for research and treatment of cancer (EORTC). Int J Radiat Oncol Biol Phys 31:1341–1346CrossRefPubMedGoogle Scholar
  10. 10.
    Pavy JJ, Denekamp J, Letschert J et al (1995) Late effects toxicity scoring: the SOMA scale. Int J Radiat Oncol Biol Phys 31:1042–1049Google Scholar
  11. 11.
    Zelefsky MJ, Levin EJ, Hunt M et al (2008) Incidence of late rectal and urinary toxicities after three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Biol Phys 70:1124–1129CrossRefPubMedGoogle Scholar
  12. 12.
    Thompson IM, Tangen CM, Paradelo J et al (2009) Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases, improves survival: long-term followup of a randomized clinical trial. J Urol 181(3):956–962CrossRefPubMedGoogle Scholar
  13. 13.
    Wilt TJ, MacDonald R, Rutks I, Shamliyan TA, Taylor BC, Kane RL (2008) Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med 148:435–448PubMedGoogle Scholar
  14. 14.
    Pickett B, Kurhanewicz J, Pouliot J et al (2006) Three-dimensional conformal external beam radiotherapy compared with permanent prostate implantation in low-risk prostate cancer based on endorectal magnetic resonance spectroscopy imaging and prostate-specific antigen level. Int J Radiat Oncol Biol Phys 65:65–72CrossRefPubMedGoogle Scholar
  15. 15.
    Potters L, Morgenstern C, Calugaru E et al (2005) 12-year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urol 173:1562–1566CrossRefPubMedGoogle Scholar
  16. 16.
    Zelefsky MJ, Wallner KE, Ling CC et al (1999) Comparison of the 5-year outcome and morbidity of three-dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer. J Clin Oncol 17:517–522PubMedGoogle Scholar
  17. 17.
    Zelefsky MJ, Cowen D, Fuks Z et al (1999) Long term tolerance of high dose three-dimensional conformal radiotherapy in patients with localized prostate carcinoma. Cancer 85(11):2460–2468CrossRefPubMedGoogle Scholar
  18. 18.
    Zietman AL, DeSilvio ML, Slater JD et al (2005) Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial. JAMA 294(10):1233–1239CrossRefPubMedGoogle Scholar
  19. 19.
    Lawton CA, Won M, Pilepich MV et al (1991) Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706. Int J Radiat Oncol Biol Phys 21:935–939CrossRefPubMedGoogle Scholar
  20. 20.
    Peeters ST, Heemsbergen WD, Koper PC et al (2006) Dose-response in radiotherapy for localized prostate cancer: results of the Dutch multicenter randomized phase III trial comparing 68 Gy of radiotherapy with 78 Gy. J Clin Oncol 24:1990–1996CrossRefPubMedGoogle Scholar
  21. 21.
    Peeters ST, Heemsbergen WD, van Putten WL et al (2005) Acute and late complications after radiotherapy for prostate cancer: results of a multicenter randomized trial comparing 68 Gy to 78 Gy. Int J Radiat Oncol Biol Phys 61:1019–1034CrossRefPubMedGoogle Scholar
  22. 22.
    Chong KT, Hampson NB, Corman JM (2005) Early hyperbaric oxygen therapy improves outcome for radiation-induced hemorrhagic cystitis. Urology 65(4):649–653CrossRefPubMedGoogle Scholar
  23. 23.
    Zelefsky MJ, Yamada Y, Cohen GN et al (2007) Five-year outcome of intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 67:65–70CrossRefPubMedGoogle Scholar
  24. 24.
    Zelefsky MJ, Hollister T, Raben A, Matthews S, Wallner KE (2000) Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer. Int J Radiat Oncol Biol Phys 47:1261–1266CrossRefPubMedGoogle Scholar
  25. 25.
    Chen AB, D’Amico AV, Neville BA, Earle CC (2006) Patient and treatment factors associated with complications after prostate brachytherapy. J Clin Oncol 24:5298–5304CrossRefPubMedGoogle Scholar
  26. 26.
    Anderson JF, Swanson DA, Levy LB et al (2009) Urinary side effects and complications after permanent prostate brachytherapy: the MD Anderson cancer center experience. Urology 74:601–605CrossRefPubMedGoogle Scholar
  27. 27.
    Sarosdy MF (2004) Urinary and rectal complications of contemporary permanent transperineal brachytherapy for prostate carcinoma with or without external beam radiation therapy. Cancer 101:754–760CrossRefPubMedGoogle Scholar
  28. 28.
    Hussain SA, Stocken DD, Peake DR et al (2004) Long-term results of a phase II study of synchronous chemoradiotherapy in advanced muscle invasive bladder cancer. Br J Cancer 90:2106–2111PubMedGoogle Scholar
  29. 29.
    Efstathiou JA, Bae K, Shipley WU et al (2009) Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol 27:4055–4061CrossRefPubMedGoogle Scholar
  30. 30.
    Hagan MP, Winter KA, Kaufman DS et al (2003) RTOG 97–06: Initial report of a phase I–II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy. Int J Radiat Oncol Biol Phys 57:665–672CrossRefPubMedGoogle Scholar
  31. 31.
    Milosevic M, Gospodarowicz M, Zietman A et al (2007) Radiotherapy for bladder cancer. Urology 69:80–92CrossRefPubMedGoogle Scholar
  32. 32.
    Gogna NK, Matthews JH, Turner SL et al (2006) Efficacy and tolerability of concurrent weekly low dose cisplatin during radiation treatment of localised muscle invasive bladder transitional cell carcinoma: a report of two sequential Phase II studies from the Trans Tasman Radiation Oncology Group. Radiother Oncol 81:9–17CrossRefPubMedGoogle Scholar
  33. 33.
    Fokdal L, Hoyer M, Meldgaard P, von der Maase H (2004) Long-term bladder, colorectal, and sexual functions after radical radiotherapy for urinary bladder cancer. Radiother Oncol 72:139–145CrossRefPubMedGoogle Scholar
  34. 34.
    Henningsohn L, Wijkstrom H, Dickman PW, Bergmark K, Steineck G (2002) Distressful symptoms after radical radiotherapy for urinary bladder cancer. Radiother Oncol 62:215–225CrossRefPubMedGoogle Scholar
  35. 35.
    Majewski W, Tarnawski R (2009) Acute and late toxicity in radical radiotherapy for bladder cancer. Clin Oncol (R Coll Radiol) 21:598–609Google Scholar
  36. 36.
    Hoskin PJ, Rojas AM, Phillips H, Saunders MI (2005) Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide. Cancer 103:2287–2297CrossRefPubMedGoogle Scholar
  37. 37.
    Cowan RA, McBain CA, Ryder WD et al (2004) Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. Int J Radiat Oncol Biol Phys 59:197–207CrossRefPubMedGoogle Scholar
  38. 38.
    Kaufman DS, Winter KA, Shipley WU et al (2009) Phase I-II RTOG study (99–06) of patients with muscle-invasive bladder cancer undergoing transurethral surgery, paclitaxel, cisplatin, and twice-daily radiotherapy followed by selective bladder preservation or radical cystectomy and adjuvant chemotherapy. Urology 73:833–837CrossRefPubMedGoogle Scholar
  39. 39.
    Duncan W, Quilty PM (1986) The results of a series of 963 patients with transitional cell carcinoma of the urinary bladder primarily treated by radical megavoltage X-ray therapy. Radiother Oncol 7:299–310CrossRefPubMedGoogle Scholar
  40. 40.
    Pos FJ, Horenblas S, Lebesque J et al (2004) Low-dose-rate brachytherapy is superior to high-dose-rate brachytherapy for bladder cancer. Int J Radiat Oncol Biol Phys 59:696–705CrossRefPubMedGoogle Scholar
  41. 41.
    Ramsey S, Tepper JE (2007) Rectal cancer radiotherapy. Cancer J 13:204–209CrossRefPubMedGoogle Scholar
  42. 42.
    Martling A, Holm T, Johansson H, Rutqvist LE, Cedermark B (2001) The Stockholm II trial on preoperative radiotherapy in rectal carcinoma: long-term follow-up of a population-based study. Cancer 92:896–902CrossRefPubMedGoogle Scholar
  43. 43.
    Improved survival with preoperative radiotherapy in resectable rectal cancer (1997) Swedish rectal cancer trial. N Engl J Med 336:980–987CrossRefGoogle Scholar
  44. 44.
    Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740CrossRefPubMedGoogle Scholar
  45. 45.
    McIntyre JF, Eifel PJ, Levenback C, Oswald MJ (1995) Ureteral stricture as a late complication of radiotherapy for stage IB carcinoma of the uterine cervix. Cancer 75:836–843CrossRefPubMedGoogle Scholar
  46. 46.
    Takeshi K, Katsuyuki K, Yoshiaki T et al (1998) Definitive radiotherapy combined with high-dose-rate brachytherapy for Stage III carcinoma of the uterine cervix: retrospective analysis of prognostic factors concerning patient characteristics and treatment parameters. Int J Radiat Oncol Biol Phys 41:319–327CrossRefPubMedGoogle Scholar
  47. 47.
    Eifel PJ, Levenback C, Wharton JT, Oswald MJ (1995) Time course and incidence of late complications in patients treated with radiation therapy for FIGO stage IB carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 32:1289–1300CrossRefPubMedGoogle Scholar
  48. 48.
    Lorvidhaya V, Tonusin A, Changwiwit W et al (2000) High-dose-rate afterloading brachytherapy in carcinoma of the cervix: an experience of 1992 patients. Int J Radiat Oncol Biol Phys 46:1185–1191CrossRefPubMedGoogle Scholar
  49. 49.
    Kapp KS, Stuecklschweiger GF, Kapp DS, Poschauko J, Pickel H, Hackl A (1997) Carcinoma of the cervix: analysis of complications after primary external beam radiation and Ir-192 HDR brachytherapy. Radiother Oncol 42:143–153CrossRefPubMedGoogle Scholar
  50. 50.
    Green JA, Kirwan JM, Tierney JF et al (2001) Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet 358:781–786CrossRefPubMedGoogle Scholar
  51. 51.
    Nishimura T, Suzuki K, Iijima M et al (2000) Spontaneous rupture of bladder diverticulum after postoperative radiotherapy for carcinoma of the uterine cervix: a case report. Radiat Med 18:261–265PubMedGoogle Scholar
  52. 52.
    Small W Jr, Du Bois A, Bhatnagar S et al (2009) Practice patterns of radiotherapy in endometrial cancer among member groups of the gynecologic cancer intergroup. Int J Gynecol Cancer 19:395–399CrossRefPubMedGoogle Scholar
  53. 53.
    Creutzberg CL, van Putten WL, Koper PC et al (2000) Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post operative radiation therapy in endometrial carcinoma. Lancet 355:1404–1411CrossRefPubMedGoogle Scholar
  54. 54.
    Keys HM, Roberts JA, Brunetto VL et al (2004) A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol 92:744–751CrossRefPubMedGoogle Scholar
  55. 55.
    Kucera H, Vavra N, Weghaupt K (1990) Benefit of external irradiation in pathologic stage I endometrial carcinoma: a prospective clinical trial of 605 patients who received postoperative vaginal irradiation and additional pelvic irradiation in the presence of unfavorable prognostic factors. Gynecol Oncol 38:99–104CrossRefPubMedGoogle Scholar
  56. 56.
    Irwin C, Levin W, Fyles A, Pintilie M, Manchul L, Kirkbride P (1998) The role of adjuvant radiotherapy in carcinoma of the endometrium-results in 550 patients with pathologic stage I disease. Gynecol Oncol 70:247–254CrossRefPubMedGoogle Scholar
  57. 57.
    Nguyen TV, Petereit DG (1998) High-dose-rate brachytherapy for medically inoperable stage I endometrial cancer. Gynecol Oncol 71:196–203CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Department of Urologic SurgeryUniversity of MinnesotaMinneapolisUSA

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